The National Institute of Standards and Technology (NIST) is a non-regulatory agency of the United States Department of Commerce which exists to promote scientific advancement of science through the use of measurement standards. Consistent with its mission, NIST has been at the forefront of research for developing “phantom” test objects to ensure the reliability of rapidly advancing imaging technologies.
Medical imaging devices and systems must be calibrated to ensure uniformity and reliability of test results. Calibration is necessary to ensure the highest possible degree of accuracy for all data obtained through imaging. Calibration may require the use of a sample or an object on which testing or imaging can be performed. With respect to human tissue and fragile or volatile test materials, it is useful to have a structure which may emulate the physical characteristics of the material on which imaging is to be performed for purposes of calibrating the imaging instruments.
A “phantom” test target is an object that simulates the structure of the tissue or other materials for which an imaging device or system is used for a system under test. The phantom test target is created to replicate structural characteristics of the tissue or the other materials for which the imaging device is used. Phantom test targets are used for calibration inter-laboratory comparison, and standardization of imaging platforms. They are also used for the validation of physical models and simulations to quantitatively interpret the image data.
There are more than 30 imaging modalities that currently utilize tissue phantoms. The phantom test targets ensure the reliability of medical imaging systems and scientifically advance the levels of accuracy that medical imaging technologies can achieve.
The phantom test targets are scanned or imaged by an imaging system under test to calibrate the performance of the imaging devices known in the art. The phantom test targets can mitigate the need to have the tissue or the other materials available for calibration (e.g., a tissue donor, live subject, cadaver or samples of organic or inorganic material).
Optical coherence tomography (OCT) is an imaging technology that uses near-infrared light. OCT captures micrometer-resolution, three-dimensional images from within the tissue or the other materials. The use of relatively long wavelength light allows it to penetrate into the tissue or the other materials. The materials imaged are sometimes referred to as light scattering medium.
Light scattering is the deflection of light due to irregularities in the propagation medium or in the interface between two media.
Scattering of light depends on the wavelength or frequency of the light being scattered. Visible light has wavelength on the order of a micrometer.
OCT can achieve sub-micrometer image resolution by using very wide-spectrum sources emitting over a ˜100 nm wavelength range. Frequency-domain optical coherence tomography is a form of OCT, which reduces signal-to-noise ratios, permitting faster signal acquisition. Another imaging modality at higher resolutions for in vivo applications is confocal microscopy, which enables the visualization of superficial layers at a depth of up to a few hundred micrometers with sub-micrometer resolution.
OCT systems have widespread commercial applicability for art and material conservation and diagnostic medicine. For example, OCT is frequently used in ophthalmology where it can be used to obtain detailed images from within the retina. OCT is also used in oncology and in interventional cardiology to help diagnose coronary artery disease.
To produce traceable and verifiable results, a tissue phantom must have well-controlled optical properties (refractive index, scattering coefficient, anisotropy factor, and absorption coefficient). Tissue phantoms are used to measure instrument characteristics such as point spread functions (PSFs) for the evaluation of lateral and axial resolutions, spectral responsivity for quantitative analyses of fluorescence and wavelength-dependent scattering, and detection sensitivity and dynamic range for tissue type-dependent optical densities and molecular concentration of target and image-contrast probes.
Phantoms made from polymeric materials are known in the art. Polymers are routinely used because of their general biocompatibility. Polymers also have the ability to form stable matrices that allow easy inclusion of various entities (e.g. polymer microparticles, cellular constituents, dyes), and tunability of absorption and scattering characteristics.
However, there are several problems known in the art with respect to the fabrication of tissue phantoms. There is no existing process for forming standard uniform tissue phantoms for accurate optical device inter-comparison.
One problem known in the art is the lack of uniformity in the use of phantom fabrication materials.
Calibration standards are necessary for both lateral and axial resolution. The United States Air Force (USAF) provides a test chart for lateral resolution calibration, using the widely accepted MIL-STO-I 50A standard. The standards provides a pattern of alternating dark/bright line pairs of decreasing periodicity with dimensions ranging from 4 μm to 1 mm to test the quality of the optical system. However, this standard is inapplicable to axial resolution.
Axial resolution calibration is particularly important for depth-resolving optical systems such as OCT and confocal microscopy. There is currently no widely accepted standard for axial resolution in the scientific community.
A standard, replicable phantom tissue test target is particularly needed in the field of ophthalmology. OCT is used to acquire optical biopsies of the retinal layers. Highly accurate quantitative thickness measurements of nerve fiber layer along with other intra-retinal layers facilitate diagnosis of conditions such as age-related macular degeneration, diabetic retinopathy, epi-retinal membranes, and glaucoma.
It is desirable to have a phantom test structure to have uniformity of surfaces and interfaces that produce light scattering. This characteristic is called optical uniformity. Optical uniformity greatly enhances the precision and accuracy of calibration.
It is desirable to have a phantom tissue test target which achieves optical uniformity and advances OCT calibration and diagnostic science.
TERMS OF ART
As used herein, the term “axial layer position” means the position of a microsphere relative to the surface of a monolayer which determines the surface profile layer.
As used herein, the term “bulk” means multiple.
As used herein, the term “calibration” means testing of any metric.
As used herein, the term “light-scattering” refers to the phenomena by which a physical deviation in a medium or surface deflects light in a detectable manner.
As used herein, the term “microsphere” means contoured or spherical particles with diameters measured in micrometer range. Microspheres may be hollow or solid and of uniform and varying sizes.
As used herein, the term “modified glass substrate” means a glass substrate that has been washed, coated or chemically treated with a solution or which has been heated or cooled chemically to alter the electrical or other properties of its surface, such a polyelectrolyte multilayer (PEM).
As used herein, the term “monolayers” means a layer or substrate of any solid, liquid or gas material which may or may not include or be in contact with microspheres.
As used herein, the term “OCT” or “optical coherent tomography” means any imaging device system capable of being calibrated using a phantom test target, and is not limited to technologies specifically referred to by this acronym.
As used herein, the term “optical uniformity” or “optical conformity” means the process or characteristic of having replicable light diffusing characteristics with minimal interference from surface irregularities.
As used herein, the term “particle flux” means particle movement within a meniscus or on a surface of a substrate.
As used herein, the term “PEM” means polyelectrolyte multilayer.
As used herein, the term “phantom” means a structure which emulates light scattering characteristics of organic or inorganic material which is tested or device system under test.
As used herein, the term “plurality” means two or more.
As used herein, the term “PDMS” or “PDMS elastomer” means a silicone-oil-based polymer having viscoelastic properties, and includes other materials.
As used herein, the term “polymer” means a polymer having viscoelastic properties.
As used herein, the term “polystyrene” means a synthetic resin that is a polymer of styrene.
As used herein, the term “PS microspheres” means microspheres made from polystyrene.
As used herein, the term “test measurement data” means any data which can be obtained using an optical imaging instrument.
As used herein, the term “test target” means a calibrated testing structure with structural properties that are inherently created by a method which uses data values.
As used herein, the term “viscoelastic” refers to the properties of materials (e.g., viscous and elastic responses) or are an intermediate of both liquids and solids in character.